We propose to thoroughly investigate the human and simian immune response to infection by HIV1 and SIV1, respectively. Recombinant DNA expression libraries that express small random segments of HIV and SIV DNA will be probed with antibodies and T cell clones from infected individuals in order to elucidate systematically HIV and SIV sequences that encode protein epitopes. The T lymphocyte response to specific retroviral antigens will be quantitated using recombinant proteins and limiting dilution analysis. The cellular targets of killing by cytotoxic T lymphocytes will be investigated in collaboration with Dr. Herman Eisen (MIT) and Dr. Robert Schooley (MGH). A complete catalogue of this information is likely to be important for the development of the most efficacious AIDS vaccine. This catalogue, coupled with immunological and molecular biological data obtained from other components of the group, will be used to formulate candidate subunit vaccines for AIDS. We also propose to create a novel vaccine vehicle using Mycobacterium bovis BCG that can express HIV antigens and stimulate long lived immunity. This delivery vehicle will be constructed by developing the molecular genetic technology necessary to introduce and express HIV DNA in BCG. BCG has a number of advantage over other vaccine vehicles in that it is currently one of the most widely used and safest human vaccines and has already been used to stimulate immunity to other human pathogens.